tbuckley/cabot-search huggingface dataset:
Net Clinical Benefit as Measure of Treatment Benefit Among Older Adults With Advanced Incurable Non–Small Cell Lung Cancer
Authors: Chee Khoon Lee, Elizabeth Driscoll
Journal: JAMA Oncology (2023)

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How to avoid intraoperative and postoperative complications in maxillary sinus elevation
Authors: Tiziano Testori, Lorenzo Tavelli, Riccardo Scaini, Alberto Maria Saibene, Giovanni Felisati, Shayan Barootchi, Ann Marie Decker, Matteo Antonio Deflorian, Gabriele Rosano, Stephen S. Wallace, Giovanni Zucchelli, Luca Francetti, Hom‐Lay Wang
Journal: Periodontology 2000 (2023)

Abstract Maxillary sinus floor elevation, via the lateral approach, is one of the most predictable bone augmentation procedures performed in implant dentistry. but both intra‑ and postoperative complications can occur, and some of them are severe. Our aim is as follows: To review the pertinent literature on the topic, especially assessing the risk factors related to complications. To give clinical recommendations to minimize intra‑ and postoperative complications with the ultimate scope of improving the standard of clinical care and patient safety.
Gold nanoparticles and gold nanorods in the landscape of cancer therapy
Authors: Prashant Kesharwani, Ruiyang Ma, Liang Sang, Mahak Fatima, Afsana Sheikh, Mohammed A. S. Abourehab, Neelima Gupta, Zhe-Sheng Chen, Yun Zhou
Journal: Molecular Cancer (2023)

Abstract Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.
Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis
Authors: Ana María Gómez-Pérez, Patricia Ruiz-Limón, Jordi Salas-Salvadó, Jesús Vioque, Dolores Corella, Montse Fitó, Josep Vidal, Alessandro Atzeni, Laura Torres-Collado, Andrea Álvarez-Sala, María Ángeles Martínez, Albert Goday, David Benaiges, Jesús García-Gavilán, María Rosa Bernal López, Isabel Moreno-Indias, Francisco J. Tinahones
Journal: Gut Microbes (2023)

To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis−4 score (FIB−4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (−24.9 to −7.51), T2 (−7.5 to −1.86), T3 (−1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB−4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB−4 tertile of change: T1 (−89.60 to −5.57), T2 (−5.56 to 11.4), and T3 (11.41 to 206.24). FIB−4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB−4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
<i>Akkermansia muciniphila</i> inhibits nonalcoholic steatohepatitis by orchestrating TLR2-activated γδT17 cell and macrophage polarization
Authors: Yuqiu Han, Qi Ling, Li Wu, Xiaosen Wang, Zhifei Wang, Jun Chen, Zhipeng Zheng, Ziyuan Zhou, Longfei Jia, Lanjuan Li, Baohong Wang
Journal: Gut Microbes (2023)

Current evidence indicates that the next-generation probiotic Akkermansia muciniphila (A. muciniphila) has therapeutic potential for nonalcoholic fatty liver disease (NAFLD), especially its inflammatory stage known as nonalcoholic steatohepatitis (NASH). However, the mechanisms of A. muciniphila in NASH prevention remain unknown. Here, A. muciniphila supplementation prevented hepatic inflammation in high-fat diet-induced NASH mice, characterized by reduced hepatic proinflammatory macrophages (M1) and γδT and γδT17 cells. Consistently, hepatic M1 and γδT cells were enriched in biopsy-proven NASH patients and high-fat/high-carbohydrate diet-induced NASH mice. Antibiotics reduced hepatic M1, γδT and γδT17 cells in NASH mice. Furthermore, A. muciniphila inhibited intestinal barrier disruption and accordingly downregulated hepatic Toll-like receptor 2 (TLR2) expression in NASH mice. The activation of TLR2 by lipoteichoic acid enriched hepatic γδT17 cells (not M1) in normal diet-fed mice and neutralized the γδT cell-lowering and liver inflammation-protecting effects of A. muciniphila in NASH mice. Additionally, activated γδT cells could promote macrophage polarization via IL−17. Our study first supported that A. muciniphila prevented NASH by modulating TLR2-activated γδT17 cells and further macrophage polarization, facilitating clinical therapeutic applications.
Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading
Authors: Peder Berg, Tobias Jensen, Jesper Frank Andersen, Samuel L Svendsen, Ida Maria Modvig, Tobias Wang, Sebastian Frische, Billy K. C. Chow, Hans Malte, Jens Juul Holst, Mads Vaarby Sørensen, Jens Leipziger
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement During acute base excess, the renal collecting duct β -intercalated cells ( β -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of β -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in β -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. Background The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid–base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. Methods We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. Results In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Conclusions Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.
Impact of intensified prevention measures on rates of hospital-acquired bloodstream infection in medical-surgical intensive care units, Israel, 2011 to 2019
Authors: Debby Ben-David, Azza Vaturi, Liat Wulffhart, Elizabeth Temkin, Ester Solter, Yehuda Carmeli, Mitchell J Schwaber
Journal: Eurosurveillance (2023)

Background Central line-associated bloodstream infection (CLABSI) is among the most common preventable infectious complications in patients in intensive care units (ICU). In 2011, the Israel National Center for Infection Control initiated a nationwide CLABSI prevention programme. Aim To evaluate the impact of different components of the programme on CLABSI and non-CLABSI rates in medical-surgical ICUs. Methods We included data collected from all 29 medical-surgical ICUs in Israel from November 2011 to December 2019. The study period was divided into three phases: I (baseline, initial CLABSI prevention guidelines introduced, initial feedback on rates provided), II (initial guidelines widely implemented, surveillance undertaken, feedback continued) and III (after implementation of additional prevention measures). Interrupted time series analysis was used to compare CLABSI and non-CLABSI rates during the three phases. Results The pooled mean (SD) incidence of CLABSI per 1,000 central line-days dropped from 7.4 (0.38) in phase I to 2.1 (0.13) in phase III (p &lt; 0.001). The incidence rate ratio (IRR) was 0.63 (95% CI: 0.51–0.79) between phases I and II, and 0.78 (95% CI: 0.59–1.02) between phases II and III. The pooled mean (SD) incidence of non-CLABSI per 1,000 patient-days declined from 5.3 (0.24) in phase I to 3.4 (0.13) in phase III (p &lt; 0.001). Conclusion National CLABSI prevention guidelines, surveillance and feedback resulted in significant reductions in CLABSI and non-CLABSI rates. In the wake of further interventions, significant reduction was achieved in ICUs reporting improvement in the uptake of additional prevention measures.
In-Hospital Deaths From Ambulatory Care–Sensitive Conditions Before and During the COVID-19 Pandemic in Japan
Authors: Kazuhiro Abe, Ichiro Kawachi, Arisa Iba, Atsushi Miyawaki
Journal: JAMA Network Open (2023)

Importance The COVID-19 pandemic may have played a role in the deterioration of access to medical care for ambulatory care–sensitive conditions (ACSCs). Objective To ascertain whether the number of in-hospital deaths and in-hospital mortality rate associated with ACSC changed after the declaration of the COVID-19 national state of emergency in Japan. Design, Setting, and Participants This cohort study used a difference-in-differences design to compare outcomes for ACSC in the period before (January 1, 2015, to December 31, 2019) vs the period after (January 1, 2020, to December 31, 2020) Japan declared a national state of emergency for the COVID-19 pandemic. Analyses used discharge summary data from 242 acute care hospitals across Japan. The sample comprised unscheduled hospitalizations of patients with ACSC during the study period (January 1, 2015, to December 31, 2020). Data analyses were performed between August 16 and December 7, 2022. Exposure The declaration of the COVID-19 national state of emergency announced by the Japanese government in April 2020 was considered to be an exogenous shock. Main Outcomes and Measures Primary outcomes were the ACSC-associated number of in-hospital deaths, number of hospitalizations, and in-hospital mortality rate. Results A total of 28 321 ACSC-related hospitalizations were observed involving 15 318 males (54.1%), with a median (IQR) age of 76 (58-85) years. The number of in-hospital deaths was 2117 (7.5%). The number of hospitalizations decreased overall (incidence rate ratio [IRR], 0.84; 95% CI, 0.75-0.94), for chronic conditions (IRR, 0.84; 95% CI, 0.77-0.92), and for vaccine-preventable conditions (IRR, 0.58; 95% CI, 0.44-0.76). However, in-hospital deaths (IRR, 1.66; 95% CI, 1.15-2.39) and in-hospital deaths within 24 hours of hospital arrival (IRR, 7.27 × 10 6 ; 95% CI, 1.83 × 10 6 to 2.89 × 10 7 ) increased for acute conditions. The in-hospital mortality rate increased for acute conditions (IRR, 1.71; 95% CI, 1.16-2.54), and the 24-hour in-hospital mortality rates also increased overall (IRR, 1.87; 95% CI, 1.19-2.96), for acute conditions (IRR, 2.15 × 10 6 ; 95% CI, 5.25 × 10 5 to 8.79 × 10 6 ), and for vaccine-preventable conditions (IRR, 4.64; 95% CI, 1.28-16.77). Conclusions and Relevance This cohort study found that in Japan, the number of in-hospital deaths increased after the declaration of the COVID-19 national state of emergency in 2020, particularly for acute ACSC and deaths within 24 hours of hospital admission. This finding suggests that access to good-quality primary care and inpatient care for patients with acute ACSC may have been compromised during the pandemic.
Rating analysis and BERTopic modeling of consumer versus regulated mHealth app reviews in Germany
Authors: Marie Uncovska, Bettina Freitag, Sven Meister, Leonard Fehring
Journal: npj Digital Medicine (2023)

Germany introduced prescription-based mobile health (mHealth) apps in October 2020, becoming the first country to offer them fully reimbursed by health insurance. These regulated apps, known as DiGAs, undergo a rigorous approval process similar to pharmaceuticals, including data protection measures and sometimes clinical trials. This study compares the user experience of DiGAs with non-prescription mHealth apps in Germany, analyzing both average app store ratings and written reviews. Our study pioneers the use of BERTopic for sentiment analysis and topic modeling in the mHealth research domain. The dataset comprises 15 DiGAs and 50 comparable apps, totaling 17,588 German-language reviews. Results reveal that DiGAs receive higher contemporary ratings than non-regulated apps (Android: 3.82 vs. 3.77; iOS: 3.78 vs. 3.53; p < 0.01; non-parametric Mann-Whitney-Wilcoxon test). Key factors contributing to positive user experience with DiGAs are customer service and personalization (15%) and ease of use (13%). However, challenges for DiGAs include software bugs (24%) and a cumbersome registration process (20%). Negative user reviews highlight concerns about therapy effectiveness (11%). Excessive pricing is the main concern for the non-regulated group (27%). Data privacy and security receive limited attention from users (DiGAs: 0.5%; comparators: 2%). In conclusion, DiGAs are generally perceived positively based on ratings and sentiment analysis of reviews. However, addressing pricing concerns in the non-regulated mHealth sector is crucial. Integrating user experience evaluation into the review process could improve adherence and health outcomes.
Wnt Signaling Stimulates Cooperation between GREB1 and HNF4α to Promote Proliferation in Hepatocellular Carcinoma
Authors: Shinji Matsumoto, Akikazu Harada, Minami Seta, Masayuki Akita, Hidetoshi Gon, Takumi Fukumoto, Akira Kikuchi
Journal: Cancer Research (2023)

Wnt signaling is known to maintain two cell states, hepatocyte differentiation and proliferation, in hepatocellular carcinoma (HCC). On the other hand, activation of Wnt signaling in colon cancer promotes uncontrollable stereotypic proliferation, whereas cells remain undifferentiated. To elucidate the unique mode of Wnt signaling in HCC, we comprehensively investigated HCC-specific Wnt pathway target genes and identified GREB1. Wnt signaling induced expression of GREB1 coupled with HNF4α and FOXA2, master transcription factors that maintain hepatic differentiation. Moreover, GREB1 was enriched at the regulatory region of atypical HNF4α target genes, including progrowth genes, thereby stimulating HCC proliferation. Therefore, GREB1 acts as a unique mediator of versatile Wnt signaling in HCC progression, bridging the roles of the Wnt pathway in differentiation and proliferation.GREB1 is a liver cancer-specific Wnt signaling target gene that induces an oncogenic shift of HNF4α, a putative tumor suppressor, and may represent a therapeutic target in Wnt-activated hepatocellular carcinoma.
Integrating On-Treatment Modified Glasgow Prognostic Score and Imaging to Predict Response and Outcomes in Metastatic Renal Cell Carcinoma
Authors: Jonas Saal, Tobias Bald, Markus Eckstein, Damian J. Ralser, Manuel Ritter, Peter Brossart, Viktor Grünwald, Michael Hölzel, Jörg Ellinger, Niklas Klümper
Journal: JAMA Oncology (2023)

In the era of immuno-oncology, imaging alone seems to be insufficient to capture treatment responses, as patients with stable disease treated with immunotherapy have a wide range of clinical outcomes. There is an unmet need for complementary (ideally cost-efficient) markers that enable assessment of therapy response and outcomes in conjunction with imaging.To examine whether longitudinal changes in the modified Glasgow prognostic score (mGPS), which is based on C-reactive protein and albumin, can predict responses and outcomes in patients with metastatic renal cell carcinoma (mRCC).This post hoc analysis, conducted from October 2022 to April 2023, evaluated the prognostic and predictive performance of on-treatment mGPS in patients with mRCC being treated with atezolizumab (plus bevacizumab) or sunitinib in 2 randomized clinical trials: the phase 3 IMmotion151 study (discovery cohort) and the phase 2 IMmotion150 study (validation cohort).Outcomes were investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 and overall survival (OS) for survival analyses. To compare the prognostic value of the on-treatment mGPS with radiologic staging, we used RECIST assessed by the Independent Review Committee (IRC-RECIST) to ensure high data quality.Of the 915 patients with mRCC in the IMmotion151 discovery cohort, baseline mGPS was available for 861 patients and on-treatment mGPS for 691. The IMmotion150 validation cohort included 305 patients with mRCC, and on-treatment mGPS could be evaluated for 199. In the IMmotion150 study, on-treatment mGPS predicted outcomes as early as 6 weeks following therapy initiation, thereby opening a window for early therapy adjustments. In both clinical trials, on-treatment mGPS provided valuable prognostic information regardless of imaging-assessed treatment response at first staging. Of note, in the disease control subgroup, on-treatment mGPS exhibited superior and independent prognostic information compared with IRC-RECIST (available for 611 patients; C-index, 0.651 [95% CI, 0.588-0.714] for the mGPS during treatment vs 0.574 [95% CI, 0.528-0.619] for IRC-RECIST).These data support the concept of integrating on-treatment mGPS for more holistic and patient-centered therapy monitoring in addition to radiologic staging to improve clinical care at a low cost for patients with mRCC.
The cost‐effectiveness of dapagliflozin in heart failure with preserved or mildly reduced ejection fraction: A <scp>European</scp> health‐economic analysis of the <scp>DELIVER</scp> trial
Authors: David Booth, Jason A. Davis, Phil McEwan, Scott D. Solomon, John J.V. McMurray, Rudolf A. De Boer, Josep Comin‐Colet, Erasmus Bachus, Jieling Chen
Journal: European Journal of Heart Failure (2023)

Aims To determine the cost‐effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient‐level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial. Methods and results A lifetime Markov state‐transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) defined health states and monthly transition count data informed transition probabilities. Multivariable generalized estimating equations captured the incidence of HF hospitalizations and urgent HF visits, while cardiovascular deaths and all‐cause mortality were estimated using adjusted parametric survival models. Health state costs were assigned to KCCQ‐TSS quartiles (2021 British pound [GBP]/Euro) and patient‐reported outcomes were sourced from DELIVER. Future values of costs and effects were discounted according to country‐specific rates. In the UK, dapagliflozin treatment was predicted to increase quality‐adjusted life years (QALYs) and life‐years by 0.231 and 0.354, respectively, and extend the time spent in the best quartile of KCCQ‐TSS by 4.2 months. Comparable outcomes were projected for Germany and Spain. The incremental cost‐effectiveness ratios were £7761, €9540 and €5343/QALY in the UK, Germany and Spain, respectively. According to regional willingness‐to‐pay thresholds, 91%, 89% and 92% of simulations in the UK, Germany and Spain, respectively, were cost‐effective following probabilistic sensitivity analyses. Conclusion Dapagliflozin, added to usual care, is very likely cost‐effective for HF with mildly reduced or preserved ejection fraction in several European countries.
Heart Failure, Neuropathy, and Spinal Stenosis
Authors: Omar A. Welleman, Yvonne C. Schrama, Henk-Jan Boiten
Journal: JAMA (2023)

A 60-year-old patient with a history of lumbar spinal stenosis had 2 months of chest pain and shortness of breath with exertion and 3 months of toe numbness. Laboratory testing showed elevated levels of high-sensitivity troponin, brain-type natriuretic peptide, aspartate aminotransferase, and alanine aminotransferase; bone scintigraphy showed increased cardiac uptake. What is the diagnosis and what would you do next?